Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Preparation, characterization, intrinsic dissolution studies and microbiological assessment of dapsone tosylate polymorphs

Daniela Flores-Pacheco¹, Kariína Mondragón-Vásquez², Jorge G Dománguez-Chívez², Blanca Elena Duque-Montaño¹, Oscar Torres-Ángeles¹, Jesús Rívera-Islas¹

¹Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Cuernavaca 62209; ²Facultad de Bioanálisis-Campus Veracruz, Universidad Veracruzana, Agustín de Iturbide s/n esq Carmen Serdán, Veracruz 91700, México.

For correspondence:- Jesús Rívera-Islas Email: rij@uaem.mx

Accepted: 20 November 2018 Published: 26 December 2018

Citation: Flores-Pacheco D, Mondragón-Vásquez K, Dománguez-Chívez JG, Duque-Montaño BE, Torres-Ángeles O, Rívera-Islas J. Preparation, characterization, intrinsic dissolution studies and microbiological assessment of dapsone tosylate polymorphs. Trop J Pharm Res 2018; 17(12):2321-2327 doi: 10.4314/tjpr.v17i12.1

© 2018 The authors.
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Abstract

Purpose: To prepare dapsone tosylate salt (TD) and its two polymorphs (TD-I and TD-II), and study their intrinsic dissolution profiles and preliminary anti-mycobacterium activity.

Methods: The synthesized product was studied with respect to the effect of solvent selection, reaction temperature and evaporation rate on the solid phase obtained. The polymorphs were characterized using powder x-ray diffraction (PXRD), proton nuclear magnetic resonance (¹H-NMR), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). UV/Vis spectroscopy was employed for quantification of the salt, while Wood apparatus was used for dissolution studies. Microdilution assay, using a 96-well equipment, was employed for the evaluation of anti-mycobacterial activity.

Results: On analysis of the solids obtained from synthesis with PXRD, two different patterns were observed. One pattern belonged to TD-I, previously reported, and the other was a new polymorph TD-II. Solvent evaporation was important in the selective preparation of TD-I or TD-II. Analyses with DSC, TGA and ¹H-NMR revealed the absence of solvent in both solids and showed that TD-II was not a solvated salt. Spectral analysis with FT-IR demonstrated structural relationship between TD-I and TD-II. Intrinsic dissolution studies showed that both polymorphs dissolved faster than dapsone (DAP).

Conclusion: It is possible to synthesize TD and select the polymorph prepared by means of modulated solvent evaporation rate. The rank order of the intrinsic dissolution rate constants was TD-II > TD-I > DAP. The tosylate salt enhanced inhibitory effect on M. fortuitum, when compared to DAP.

Keywords: Dapsone tosylate, Polymorphism, Solid phase characteristics, Intrinsic dissolution, Anti-mycobacterium activity